Synthesis of novel hypotensive aromatic thiocarbamate glycosides

Article abstract of DOI:10.1039/a907050h

Syntheses of hypotensive thiocarbamate glycosides from Moringa oleifera are described. The route involves, first, the condensation of the sugar moiety with p-hydroxybenzonitrile to give glycoside 2, then subsequent reduction of 2 to the glycosidic benzyla

Full text of DOI:10.1039/a907050h

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Synthesis of novel hypotensive aromatic thiocarbamate glycosides
Rubeena Saleem* and Jerrold Meinwald
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca,
NY-14853, USA
1
Received (in Cambridge, UK) 31st August 1999, Accepted 13th September 1999
Syntheses of hypotensive thiocarbamate glycosides from Moringa oleifera are described. The route involves, first, the
condensation of the sugar moiety with p-hydroxybenzonitrile to give glycoside 2, then subsequent reduction of 2 to
the glycosidic benzylamine 3, which is then converted into isothiocyanate 6. Finally, alcoholysis of 6 gives the desired
thiocarbamate glycosides.
Thiocarbamate glycosides are rare in nature. They were first
isolated in 1992 by S. Faizi et al. from a well known medicinal
plant, Moringa oleifera, which is commonly found in Karachi,
Pakistan.1 These compounds exist in two stereoisomeric forms
due to the barrier to rotation about the C–N bond, which has
partial double-bond character.1,2 Biological evaluation suggests
that these glycosides are potent hypotensive,3 antispasmodic4
and antiviral5 agents. Their paucity in nature and their signifi-
cant pharmacological properties make them an attractive target
for synthesis.
In this study, we have prepared some known glycosides,
niazinin A 7 and niazimicin1 8, as well as several analogues
(9–12), in order to be able to explore the chemistry and biology
of this group of compounds more extensively. Although both E
and Z isomers of these glycosides appear to occur in nature,1
the E isomers have been obtained predominantly in the present
work. 4-(α--Rhamnosyloxy)benzylamine 3, the corresponding
dimeric secondary amine 4, and the N,O-tetra-acetyl derivative
5 prepared in this study are new, although the ortho isomer of 3
has been reported from flowers of Reseda odorata and was syn-
thesized in low yield.6 4-(α--Rhamnosyloxy)benzyl isothio-
cyanate 6, formed on the way to the thiocarbamates and
reported to be a potent antimicrobial agent,7 is prepared for the
first time.
Results and discussion
The synthetic route followed in this work is outlined in Scheme
1. After acetylation of -(ϩ)-rhamnose,8 the crude tetra-acetate
1 was condensed with p-hydroxybenzonitrile in the presence of
a Lewis acid (zinc chloride) to give pure white, crystalline
4-(2Ј,3Ј,4Ј-tri-O-acetyl-α--rhamnosyloxy)benzonitrile
2
in
65–82% yield. Although zinc chloride usually gives α- or
β- anomers predominantly, exceptions to this outcome are
known.8 Prior to this synthesis compound 2 had been prepared
only through a multistep procedure.9
After trying many methods to reduce 2 to 3, including cata-
lytic hydrogenation at 40–60 psi† and reduction with LiAlH4
(LAH)–H2SO4 (100%), sodium trifluoroacetoxyborohydride10
was found to be a suitable reagent for this reduction. The form-
ation of amine 3 is very slow, requiring 5–6 days to give crude
product, which on HPLC affords 3 in 50% yield. Not unexpec-
tedly, this reagent does not selectively reduce the nitrile group,
but also brings about deacetylation of the sugar moiety.
aromatic protons at δ 7.02 and 7.28 (Table 1) as compared with
the corresponding protons of 2 (Table 1), as well as a singlet at
δ 3.82 for the benzylic methylene group (H2-7). An HMQC
spectrum showed connectivity of H-7 with the carbon atom at
δC 53.11 (Table 3) which was recognized as a CH2 in a DEPT
13C NMR experiment. These chemical shifts, along with a
downfield shift of C-4 compared with that observed in 2,9 and
their agreement with the chemical shift observed for benzyl-
amine,11 confirm the structure of product 3. The loss of three
singlets for acetoxy methyls along with an MS fragment ion at
m/z 147 demonstrated that deacetylation of the sugar moiety
has taken place. EIMS, ESMS and CIMS of 3 did not show its
1
The H NMR spectrum of 3 showed an upfield shift for the
* Address for correspondence: Dr HMI Institute of Pharmacology
and Herbal Sciences, Hamdard University, Karachi-74600, Pakistan.
† 1 psi = 6894.7 Pa.
J. Chem. Soc., Perkin Trans. 1, 2000, 391–394
This journal is © The Royal Society of Chemistry 2000
391

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Table 1 1H NMR data of compounds 2–5: coupling constants (J/Hz) in parentheses
Protona
2
3
4
5
2,6
3,5
ArCH2
1Ј
2Ј
3Ј
4Ј
5Ј
6Ј
7.29d (8.8)
7.73d (8.8)
7.02d (8.4)
7.28d (8.4)
3.82s
5.45d (1.6)
4.03dd (1.6, 3.6)
3.85dd (3.6, 9.2)
3.46dd (9.2, 9.6)
3.59dd (9.6, 6.4)
1.13d (6.4)
7.03d (8.8)
7.29d (8.8)
3.83br s
5.45d (1.6)
4.01dd (3.6, 1.6)
3.82dd (3.6, 9.2)
3.48dd (9.2, 9.6)
3.64qd (6.4, 9.6)
1.17d (6.4)
7.03d (8.8)
7.22d (8.8)
4.27d (6.4)
5.56br s
5.75d (1.6)
5.41dd (1.6, 3.6)
5.35dd (3.6, 10.0)
5.08t (10.0)
3.91qd (6.0, 10.0)
1.11d (6.0)
5.38m
5.37dd (3.6, 9.2)
5.07dd (9.2, 9.6)
3.94qd (6.4, 9.6)
1.11d (6.4)
1.88s
2.11, 2.01, 1.94s
7.58 br s
NAc
OAc
NH
2.11, 2.01 1.83s
a Unprimed locants refer to the aromatic ring; primed locants refer to the rhamnose moiety.
ation of its N,O-tetra-acetyl derivative 5, HRCIMS of which
showed a molecular ion peak at m/z 438.1768 (calc. for
C21H28NO9, Mϩ ϩ 1: m/z, 438.1764) (vide infra). The 1H NMR
spectrum of 5 further showed downfield shifts for the sugar
moiety along with four singlets for the acetyl groups (three
O-acetyl and one N-acetyl) at δ 2.11, 2.01, 1.94 and 1.88
(Table 1).
HPLC analysis of crude 3 showed a shoulder peak, which
was identified through detailed spectral study as N,N-bis-4-(α-
-rhamnosyloxy)benzylamine 4 in 3% yield. The UV, IR and
NMR spectral data for 4 were very similar to those for 3. The
1
only difference in the H NMR spectra of the two compounds
was in the multiplicity of the benzylic methylene (H-7) which
appeared as a br s in 4 (converted into sharp singlet when
shaken with D2O) at δ 3.83 (Table 1). A molecular ion peak in
the ESMS of 4 at m/z 522 (Mϩ ϩ 1) confirmed their structural
assignment.
Equimolar quantities of 4-(α--rhamnosyloxy)benzylamine
hydrochloride and thiophosgene react to give the correspond-
ing isothiocyanate 6, in 33–55% yield. Spectral data for 6
prepared in this way were comparable to those previously
reported.12 Thiocarbamate glycosides 7–12 were obtained in
≈20–40% yield when 6 was treated with sodium alkoxides. Spec-
tral data of 7 (niazinin A) and 8 (niazimicin) were in full agree-
ment with the literature values,1 specific optical rotations of
these compounds are reported here for the first time. Structures
of naturally occurring thiocarbamate glycosidic analogues were
established by detailed spectral studies (UV, IR, MS, NMR and
2D-NMR) (Tables 1 and 3) and comparison of data with liter-
ature values1 for 7 and 8.
Experimental
Mps were taken on a capillary apparatus and are uncorrected.
UV (in MeOH) and IR (in CH2Cl2) spectra were recorded on a
Hitachi U-2010 UV/VIS and a Perkin-Elmer 16 PC FTIR
spectrophotometer, respectively. EIMS, CIMS and HRMS were
recorded on a Micromass Autospec instrument, while electro-
spray data was collected on a VG Quattro instrument. NMR
spectra were recorded in (CD3)3CO on a Varian XL-400
1
instrument operating at 400 MHz for H NMR and 100 MHz
for 13C NMR. HMQC and HMBC spectra were recorded on a
UNITY-500 instrument. Specific optical rotations (in MeOH)
were determined using a Perkin-Elmer 241 Polarimeter; [α]D-
values are given in units of 10Ϫ1 deg cm2 gϪ1. The 13C NMR
spectral assignments are based on DEPT, HMQC and HMBC
experiments as well as on comparison with reported values for
similar compounds.1,9,11,12 Purity of compounds was checked on
silica gel GF254 coated sheets. Reversed-phase high-perform-
ance liquid chromatography was performed using a semipre-
parative column (Supelco LC-18-BD; 25 cm × 10 mm; id 5 µm)
(Supelco, Bellefonte, PA), a dual pump system (Waters M-45
Scheme 1
molecular-ion peak. However, HRCIMS showed a fragment
ion [corresponding to an (M Ϫ NH2)ϩ ion] at m/z 253.1072
(calc. for C13H17O5: m/z, 253.1075). Formation of 4-(α--
rhamnosyloxy)benzylamine 3 was confirmed by the prepar-
392
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Table 2 1H NMR data for glycosides 9–12; coupling constants (J/Hz) in parentheses
Protona
9
10
11
12
2,6
3,5
ArCH2
1Ј
2Ј
3Ј
7.03d (8.8), 7.04d (8.8)
7.30d (8.8), 7.25d (8.8)
4.71d (5.2), 4.41d (6.4)
5.47br s
4.02dd (3.2, 1.6)
3.83dd (9.6, 3.2)
3.49t (9.6)
7.04d (8.8), 7.06d (8.8)
7.31d (8.8), 7.25d (8.8)
4.71d (6.0), 4.38d (6.0)
5.46d (1.6)
4.03dd (3.2, 1.6)
3.83dd (9.2, 3.2)
6.99d (8.8), 7.01d (8.8)
7.26d (8.4), 7.20d (8.4)
4.67d (5.6), 4.35d (5.6)
5.41d (1.6)
3.96dd (3.6, 1.6)
3.77dd (9.2, 3.6)
7.06d (8.8), 7.08d (8.4)
7.33d (8.8), 7.28d (8.4)
4.73d (6.0), 4.45d (6.0)
5.42br s
3.98dd (3.6, 1.6)
3.85dd (3.6, 9.6)
3.51t (9.2)
4Ј
3.49t (9.2)
3.43dd (9.6, 9.2)
5Ј
6Ј
1Љ
2Љ
3Љ
4Љ
NH
3.63qd (9.6, 6.0)
1.18d (6.0), 1.17d (6.0)
4.35t (6.4), 4.37t (6.4)
1.68m, 1.67m
3.64qd (9.2, 6.4)
3.59qd (9.6, 6.4)
3.57qd (6.0, 9.6)
1.21d (6.0), 1.20d (6.0)
4.21d (6.4), 4.22d (6.4)
2.03m
0.97d (6.8), 0.92d (6.8)
0.97d (6.8), 0.92d (6.8)
8.57br s
1.19d (6.4), 1.18d (6.4)
5.43hep (6.4), 5.41hep (6.4)
1.27d (6.4), 1.26d (6.4)
1.27d (6.4), 1.26d (6.4)
1.13d (6.4), 1.12d (6.4)
4.36t (6.4), 4.38t (6.4)
1.62quin (6.8)
1.34sextet (7.6), 1.24m
0.87t (7.6), 0.85t (7.6)
8.42br s
0.85t (7.6), 0.81t (7.6)
8.49br s
8.39br s
a Unprimed locants refer to the aromatic ring; primed locants refer to the rhamnose moiety; double-primed locants refer to the thiocarbamate ester
group.
Table 3 13C NMR chemical shifts for glycosides 3–5 and 9–12
Carbona
3
4
5
9
10
11
12
1
2,6
3,5
4
ArCH2
NC(S)OR
1Ј
2Ј
3Ј
4Ј
5Ј
6Ј
156.70
117.31
130.10
134.42
53.11
156.56
117.29
130.12
134.26
52.93
156.04
117.08
130.16
135.45
43.29
158.86, 156.79
117.32, 117.40
129.97, 129.71
132.62, 132.79
48.69, 46.57
191.97, 190.5
99.51, 99.48
71.75
72.23
73.61
70.21
18.22
156.92, 156.80
117.36, 116.05
130.00, 130.18
132.71, 132.94
48.56, 46.52
191.14
99.56, 99.51
71.80
72.34
156.93
156.91, 156.78
117.34, 117.43
130.01, 129.54
132.60, 132.81
48.72, 48.59
192.01, 190.53
99.52, 99.48
71.75
72.29
73.61
70.21
18.24
117.35, 117.41
130.00, 129.71
132.65
48.73, 46.61
192.01, 191.12
99.56
71.79
72.34
73.64
70.24
99.55
71.61
72.12
73.38
70.19
18.21
99.48
71.43
71.97
73.22
70.15
18.11
97.08
70.10
70.47
71.52
68.42
18.17
73.66
70.25
18.26
18.26
1Љ
2Љ
3Љ
72.19, 73.27
22.83, 22.74
10.63, 10.72
73.71
22.10, 21.99
70.49, 71.50
31.64, 31.58
19.82
76.75, 77.82
28.72, 28.67
19.35
4Љ
14.12
5Љ
6Љ
7Љ
NCOCH3
OCOCH3
170.45
170.89, 170.78,
170.72
NCOCH3
OCOCH3
21.03
21.12, 21.08
a Unprimed locants refer to the aromatic ring; primed locants refer to the rhamnose moiety; double-primed locants refer to the thiocarbamate ester
group.
and 510 models), an L4000 Hitachi UV detector (λ = 300 nm),
and an HP-3396A integrator. The flow was 2.5 ml minϪ1 and
runs were monitored at λ = 220 nm (in case of 3) and λ = 245
nm (in case of thiocarbamate glycosides).
MeOH 99.9% from Fisher Scientific and absolute EtOH
from Pharmaco were used. Propan-1-ol, propan-2-ol, butan-
1-ol and 2-methylpropan-1-ol from Fisher Scientific were
further dried by refluxing with Mg turnings and iodine for
1–2 h and then distilled. Tetrahydrofuran from Mallinckrodt
was distilled from potassium metal–benzophenone under
argon.
4-(2Ј,3Ј,4Ј-Tri-O-acetyl-ꢀ-L-rhamnosyloxy)benzonitrile 2
p-Hydroxybenzonitrile (1 g), rhamnose tetra-acetate 1 (1 g) and
anhydrous zinc chloride (272 mg) were heated at 160 ЊC with
stirring for 40 min. The melt after cooling was divided between
benzene (130 ml) and 1 M NaOH (100 ml). The aqueous layer
was extracted thrice with benzene (150 ml). The combined ben-
zene phase was dried over CaCl2 and evaporated on a Rotovap
to give a yellow residue, which slowly converted into white crys-
tals spontaneously (970 mg, 82%) (mp 63 ЊC; lit.,9 62 ЊC). The
UV, IR, MS and NMR spectral data of these crystals agreed
with those reported for 4-(2Ј,3Ј,4Ј-tri-O-acetyl-α--rhamno-
1
syloxy)benzonitrile 2.9 The H NMR spectrum of this product
Tetra-acetylation of L-(؉)-rhamnose
is reported in Table 1.
To a solution of -(ϩ)-rhamnose monohydrate (1 g) in pyridine
(3 ml) was added acetic anhydride (3 ml) and the reaction mix-
ture was kept overnight at ambient temperature before being
divided between ethyl acetate (100 ml) and water (100 ml). The
aqueous phase was extracted thrice with ethyl acetate (150 ml)
and the combined organic phase was washed thrice with water
(300 ml), dried over CaCl2 and evaporated under reduced pres-
sure to give crude rhamnose tetra-acetate 1 (1.87 g, 92%).8
4-(ꢀ-L-Rhamnosyloxy)benzylamine 3 and bis derivative 4
To a stirred suspension of sodium borohydride (0.5 g, 13.2 mmol)
in tetrahydrofuran (5 ml) was added trifluoroacetic acid (1.01
ml, 13.2 mmol in 10 ml of THF) over a period of 15 min at 0 ЊC
under argon. To this solution of sodium trifluoroacetoxyboro-
hydride was added compound 2 (0.5 g, 1.3 mmol in 5 ml of
THF) in a dropwise manner. The mixture was stirred for one
J. Chem. Soc., Perkin Trans. 1, 2000, 391–394
393

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day at room temperature and for another 4–5 days after the
introduction of an additional amount of reagent (0.5 g of
NaBH4 and 1.01 ml of CF3CO2H). Excess of reagent was
decomposed with saturated aq. NaCl (50 ml) at 0 ЊC, and two
layers were separated. The THF layer was dried over Na2SO4
and evaporated under reduced pressure. A small part of the
residue (200 mg/5 ml) was subjected to HPLC (mobile phase
MeOH–H2O 9:1), which showed three peaks. A broad peak 1
(tR 3.73 min, 87 mg) remained unidentified; peak 2 (tR 5.07 min)
was identified as 4-(α--rhamnosyloxy)benzylamine 3 (101 mg,
50%; Rf 0.64, MeOH) and peak 3 (tR 5.59 min) was recognized
as N,N-bis[4-(α--rhamnosyloxy)benzyl]amine 4 (6.3 mg, 3%;
Rf 0.61, MeOH).
min; Rf 0.14 (CHCl3–MeOH 9:1), 9], 25% [tR 6.76 min; Rf 0.14
(CHCl3–MeOH 9:1), 10], 33% [tR 8.77 min; Rf 0.12 (CHCl3–
MeOH 9:1), 11] and 38% [tR 8.36 min; Rf 0.12 (CHCl3–MeOH
9:1), 12], yield respectively.
O-Propyl (E)-[4-(ꢀ-L-rhamnosyloxy)benzyl]thiocarbamate 9.
[α]D Ϫ18 (c 1); λmax(MeOH)/nm 205, 223, 245; νmax(CH2Cl2)/
cmϪ1 3400, 3100, 2900, 1600, 1500, 1400 and 1260; HREIMS
(m/z) 371.1413 [calc. for C17H25NO6S: 371.1402 (M)]; EIMS
(m/z) (%) 371 (Mϩ, 0.3), 353 (0.5), 311 (1), 225 (30), 183 (22),
1
147 (10), 129 (12), 122 (15), 107 (100) and 77 (25). H and 13C
NMR data in Tables 2 and 3.
O-Isopropyl (E)-[4-(ꢀ-L-rhamnosyloxy)benzyl]thiocarbamate
10. [α]D Ϫ18.88 (c 0.9); λmax(MeOH)/nm 203, 220 and 245;
νmax(CH2Cl2)/cmϪ1 3400, 3100, 1600, 1520 and 1240; HREIMS
(m/z) 371.1383 [calc. for C17H25NO6S: 371.1402 (M)]; EIMS
(m/z) (%) 371 (Mϩ, 10), 328 (4), 225 (40), 182 (100), 166 (6), 147
(13), 129 (15), 122 (22), 107 (75) and 77 (10). 1H and 13C NMR
data in Tables 2 and 3.
4-(ꢀ-L-Rhamnosyloxy)benzylamine 3. [α]D Ϫ33.75 (c 0.8);
λmax(MeOH)/nm 201, 222 and 265; νmax(CH2Cl2)/cmϪ1 3400,
3100, 2900, 1640–1580, 1510, 1230 and 1150; HRCIMS (m/z)
253.1072 (Calc. for C13H17O5: 253.1075, M Ϫ NH2); ESMS
(ϩve) (m/z) 253; EIMS m/z (%) 253 (0.5), 147 (22), 129 (24), 107
(100) and 77 (17); 1H and 13C NMR in Tables 1 and 3.
N,N-Bis[4-(ꢀ-L-rhamnosyloxy)benzyl]amine 4. [α]D Ϫ13.88
(c 1.6); λmax(MeOH)/nm 192, 224 and 270; νmax(CH2Cl2)/cmϪ1
3050, 2950, 1630, 1580 and 1260; ESMS (ϩve) (m/z) 522
(Mϩ ϩ 1); EIMS m/z (%) 485 (0.5), 269 (0.5), 253 (1), 239 (5),
O-Butyl (E)-[4-(ꢀ-L-rhamnosyloxy)benzyl]thiocarbamate 11.
[α]D Ϫ47 (c 1); λmax(MeOH)/nm 201, 220, 245; νmax(CH2Cl2)/
cmϪ1 3400, 3100, 1620, 1500, 1230; HREIMS (m/z) 385.1549
[calc. for C18H27NO6S: 385.1559 (M)]; EIMS (m/z) (%) 385 (Mϩ,
15), 329 (1), 239 (75), 183 (85), 166 (17), 147 (19), 129 (26), 122
(30), 107 (100) and 77 (13). 1H and 13C NMR in Tables 2 and 3.
1
211 (6), 147 (22), 133 (24), 129 (25) and 107 (100); H and 13C
NMR in Tables 1 and 3.
N-Acetyl-4-[(2Ј,3Ј,4Ј-tri-O-acetyl)-ꢀ-L-rhamnosyloxy]-
benzylamine 5
O-Isobutyl (E)-[4-(ꢀ-L-rhamnosyloxy)benzyl]thiocarbamate
12. [α]D Ϫ40 (c 1); λmax(MeOH)/nm 205, 223 and 245;
νmax(CH2Cl2)/nm 3400, 3100, 2900, 1620, 1510, 1420 and 1240;
HREIMS (m/z) 385.1565 [calc. for C18H27NO6S: 385.1559
(M)]; EIMS (m/z) (%) 385 (Mϩ, 7), 329 (12), 239 (18), 183 (100),
To a solution of 3 (25 mg) in pyridine (0.5 ml) was added acetic
anhydride (0.5 ml) and the mixture was kept at room temper-
ature overnight. Usual work-up gave pure acetyl derivative 5 as
a white solid, mp 152–153 ЊC; Rf 0.52 (CHCl3–MeOH 9:1);
[α]D Ϫ25 (c 1.2); λmax(MeOH)/nm 224, 271; νmax(CH2Cl2)/cmϪ1
3100, 2950, 1740, 1660, 1600, 1510, 1420, 1380, 1260 and 1230;
HRCIMS (m/z) 438.1768 [calc. for C21H28NO9: 438.1764
(M ϩ 1)]; ESMS (ϩve) (m/z) (%) 438 (Mϩ ϩ 1, 100), 396 (20),
379 (5), 273 (95), 231 (10), 213 (25), 153 (7) and 107 (4); 1H and
13C NMR data in Tables 1 and 3.
1
147 (28), 129 (27), 122 (15), 107 (75) and 77 (7). H and 13C
NMR data in Tables 2 and 3.
Acknowledgements
We are grateful to the United States Education Foundation in
Pakistan for awarding a Fulbright Scholarship to Dr Rubeena
Saleem for the pursuit of this work in Cornell University.
4-(ꢀ-L-Rhamnosyloxy)benzyl isothiocyanate 6
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A solution of 4-(α--rhamnosyloxy)benzylamine hydrochloride
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two phases were then separated and the aqueous phase was
extracted twice with diethyl ether (30 ml). The combined
organic phase was evaporated under reduced pressure to give 6
as a yellow residue (72 mg, 53%).
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9 N. B. Bashir, S. J. Phythian, A. J. Reason and S. M. Roberts,
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4-(α--Rhamnosyloxy)benzyl isothiocyanate 6 (50 mg) was
refluxed with a freshly prepared sodium alkoxide (20 ml) for 30
min with continuous stirring. The reaction mixture was divided
between water (10 ml) and ethyl acetate (20 ml). The aqueous
phase was extracted thrice with ethyl acetate (30 ml). The com-
bined organic layer was washed with an equal amount of water
thrice, dried over CaCl2, and concentrated under reduced
pressure to give a crude product 7–12, which was further puri-
fied by HPLC. Mobile phase used for compounds 7, 10–12 was
MeOH–H2O (7:3) while that for glycosides 8 and 9 was
MeOH–H2O (1:1). HPLC of crude 7 gave pure niazinin A
(29%; tR 6.03 min); [α]D Ϫ35 (c 1). Compound 8 on HPLC
analysis gave niazimicin (22%; tR 15.27 min); [α]D Ϫ12 (c 1).
HPLC of 9–12 gave pure glycosidic analogues in 24% [tR 25.59
10 R. P. Iyer, L. R. Phillips and W. Egan, Synth. Commun., 1991, 21,
2053.
11 C. J. Pouchert and J. Behnke, The Aldrich Library of 13C and 1H FT
NMR Spectra, 1st edn., 1993, vol. 2, pp. 565 and 610.
12 F. M. Dayrit, A. D. Alcantar and I. Villasenor, Philipp. J. Sci., 1990,
119, 23.
13 A. Kjaer and K. Rubinstein, Acta Chem. Scand., 1954, 8, 598.
Paper a907050h
394
J. Chem. Soc., Perkin Trans. 1, 2000, 391–394